Bristol-Myers Squibb has announced that Sustiva® (efavirenz) has received approval from the U.S. Food and Drug Administration to include new long-term virologic and clinical data from BMS Study 006 in its prescribing information.
The new data demonstrate the long-term durability of virologic response in people living with HIV-1 who are naïve to protease inhibitors, lamivudine (3TC) and non-nucleoside reverse transcriptase inhibitors (NNRTI) through more than three years of treatment on a combination regimen containing Sustiva.
"The new data from Study 006 provide valuable information to health care professionals supporting first-line use of Sustiva-based combination therapy," said Karen Tashima, M.D., associate professor of medicine, Brown Medical School, Miriam Hospital, Providence, Rhode Island. "The long-term data suggest that patients who stay on Sustiva as part of their combination therapy may experience durable viral suppression for more than three years reinforcing its use in first-line HIV combination therapy."
BMS Study 006 was a randomized, open-label, multicenter, multinational study of 1,266 HIV-1 positive people in the United States, Europe and Canada who were naïve to protease inhibitors, lamivudine and NNRTIs and who had a viral load greater than or equal to 10,000 copies/mL and a CD4+ cell count greater than or equal to 50 cells/mm3. Patients were given one of three treatment regimens: Sustiva+zidovudine+lamivudine (EFV 600 mg once-daily+ZDV 300 mg every 12 hours+LAM 150 mg every 12 hours; n=422), or Sustiva+indinavir (EFV 600 mg once-daily+IDV 1,000 mg every 8 hours; n=429), or indinavir+zidovudine+lamivudine (IDV 800 mg every 8 hours+ZDV 300 mg every 12 hours+LAM 150 mg every 12 hours; n=415).
Through 168 weeks, the percentage of patients who achieved and maintained HIV-1 RNA less than 400 copies/mL was 48 percent (EFV+ZDV+LAM), 40 percent (EFV+IDV) and 29 percent (IDV+ZDV+LAM) using an intent-to-treat, time-to-loss of virologic response analysis. The response rate for achieving viral load less than 50 copies/mL through 168 weeks was 43 percent (EFV+ZDV+LAM), 31 percent (EFV+IDV) and 23 percent (IDV+ZDV+LAM). A Kaplan-Meier analysis of time to loss of virologic response (HIV-1 RNA less than 400 copies/mL) suggests that both the trends of virologic response and differences in response continue through four years. Kaplan-Meier is a method of statistical analysis commonly used by biomedical researchers to predict the probability of a particular outcome over a given period of time.
Patients who remained on therapy through 168 weeks demonstrated mean CD4+ cell count increases (from a median baseline of 320 cells/mm3) of 329 cells/mm3 (EFV+ZDV+LAM; n=205), 319 cells/mm3 (EFV+IDV; n=158), and 329 cells/mm3 (IDV+ZDV+LAM; n=129).
"This sNDA approval represents another important addition to the support for combination therapy containing Sustiva in treating people living with HIV-1 infection," said Anthony Hooper, president, U.S. Pharmaceuticals, Bristol-Myers Squibb Company. "Since it first became available in 1998, Sustiva has been administered to thousands of patients in combination therapy to treat their HIV-1 infection. With this new labeling, health care professionals now have additional information to draw on when creating a durable antiretroviral regimen for their treatment-naïve patients."
In the study, selected treatment-emergent adverse events of moderate or severe intensity reported in greater than or equal to 2 percent of patients treated in the EFV+ZDV+LAM (n=412) and IDV+ZDV+LAM (n=401) arms were: rash (11 percent for EFV+ZDV+LAM, 5 percent for IDV+ZDV+LAM), nausea (10 percent, 24 percent), dizziness (9 percent, 2 percent), tiredness (8 percent, 9 percent), headache (8 percent, 3 percent), trouble sleeping (7 percent, 2 percent), vomiting (6 percent, 14 percent), depression (5 percent, less than 1 percent), trouble concentrating (5 percent, less than 1 percent), upset stomach (4 percent, 6 percent), diarrhea (3 percent, 6 percent), abnormal dreams (3 percent, 0 percent), anxiety (2 percent, less than 1 percent), sleepiness (2 percent, less than 1 percent), stomach pain (2 percent, 5 percent) and nervousness (2 percent, 0 percent). More subjects discontinued the study prematurely due to adverse events in the IDV+ZDV+LAM (20 percent) arm than in either of the treatment regimens containing Sustiva (8 percent in each Sustiva arm).
Analysis of long-term data from Study 006 (median follow-up 180 weeks, 102 weeks, and 76 weeks for patients treated with EFV+ZDV+LAM, EFV+IDV, and IDV+ZDV+LAM, respectively) showed that, beyond 24 weeks of therapy, the incidence of new-onset nervous system symptoms among patients treated with Sustiva were generally similar to those in the indinavir-containing control arm.
The new labeling also indicates that Sustiva® should not be administered concurrently with voriconazole (better known as Vfend®, a drug indicated for treatment of certain fungal infections) because Sustiva significantly decreases voriconazole plasma concentrations while voriconazole significantly increases Sustiva plasma concentrations. In addition, when Sustiva is co-administered with Reyataz® (atazanavir sulfate) in treatment-naïve patients, the recommended dose of Reyataz is 300 mg with ritonavir 100 mg and Sustiva 600 mg ( all once daily). Dosing recommendations for Sustiva and Reyataz in treatment-experienced patients have not been established.